O33 Longitudinal assessment of biomarkers in NOBILITY, a randomized, phase II clinical trial of obinutuzumab for treatment of proliferative lupus nephritis

• Published in: Lupus science & medicine 2024-03, Vol.11 (Suppl 1), p.A31-A33
• Main Authors: Furie, Richard A, Tas, Sander W, Malvar, Ana, Looney, Cary M, Raghu, Harini, Anania, Veronica G, Mao, Ashley, Schindler, Thomas, Martins, Elsa, Ross Terres, Jorge A, Vital, Edward M
• Format: Article
• Language: English
• Subjects: Antibodies; Biomarkers; Creatinine; Lupus; Nobility; Oral Presentations; Stockholders
• ISSN: 2053-8790
• DOI: 10.1136/lupus-2024-el.42

ObjectiveTo investigate changes in peripheral B cells, B-cell subsets and biomarkers in NOBILITY.MethodsIn the randomized Phase II NOBILITY trial (NCT02550652), patients with lupus nephritis received standard care (MMF) plus obinutuzumab 1000 mg or placebo on Weeks 0, 2, 24 and 26. We analyzed autoantibodies, complement C3/C4, total CD19+ B cells and B-cell subsets using high-sensitivity flow cytometry at Weeks 4, 12, 24, 52, 76 and 104. Sustained B-cell depletion was defined as total B cells below the lower limit of quantitation (LLOQ; 0.4 cells/μL) at Weeks 24 and 52. Detectable B cells were defined as total B cells above LLOQ.ResultsBaseline biomarker levels were similar between treatment groups. By Week 4, 89.3% (50/56) of obinutuzumab-treated patients had total and all B-cell subsets below LLOQ; by Week 104, 91.8% (45/49) had total B cells above LLOQ. At Week 104, mean memory B cells remained low compared with baseline in obinutuzumab-treated patients (3.5 vs 65 cells/µL), whereas mean naïve B cells were repleted (127 vs 229 cells/µL; figure 1). Of 52 obinutuzumab-treated patients with B-cell measurements at Weeks 24 and 52, 61.5% had sustained B-cell depletion. A trend towards higher renal response rates at Week 76 were observed in obinutuzumab-treated patients with sustained B-cell depletion and those with detectable B cells compared with placebo-treated patients (figure 2). In patients positive for anti-dsDNA antibodies at baseline (>30 IU/mL), median anti-dsDNA antibodies at Week 104 were reduced by 84% and 39% in the obinutuzumab and placebo groups, respectively; anti-C1q antibodies were reduced by 61% and 7%, respectively. Among patients who were hypocomplementemic at baseline (C3